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1.
Int J Med Sci ; 21(7): 1353-1365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818463

RESUMO

This study aims to explore the molecular mechanisms and associated pathways of myocardial infarction (MI). We employed a variety of analytical methods, including Mendelian Randomization (MR) analysis, transcriptome microarray data analysis, gene function and pathway enrichment analysis, untargeted metabolomic mass spectrometry analysis, and gene-metabolite interaction network analysis. The MR analysis results revealed a significant impact of mitochondrial DNA copy number on MI and coronary artery bypass grafting. Transcriptome analysis unveiled numerous differentially expressed genes associated with myocardial ischemia, with enrichment observed in cardiac function and energy metabolism pathways. Metabolomic analysis indicated a significant downregulation of mitochondrial regulation pathways in ischemic myocardium. T500 metabolite quantification analysis identified 90 differential metabolites between MI and Sham groups, emphasizing changes in metabolites associated with energy metabolism. Gene-metabolite interaction network analysis revealed the significant roles of key regulatory molecules such as HIF1A, adenosine, TBK1, ATP, NRAS, and EIF2AK3, in the pathogenesis of myocardial ischemia. In summary, this study provides important insights into the molecular mechanisms of MI and highlights interactions at multiple molecular levels, contributing to the establishment of new theoretical foundations for the diagnosis and treatment of MI.


Assuntos
Adenosina , Infarto do Miocárdio , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Humanos , Adenosina/metabolismo , Metabolismo Energético/genética , Redes Reguladoras de Genes , Perfilação da Expressão Gênica , Análise da Randomização Mendeliana , DNA Mitocondrial/genética , Mitocôndrias/metabolismo , Metabolômica/métodos , Transcriptoma
2.
Int J Med Sci ; 13(3): 225-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26941583

RESUMO

BACKGROUND: Previous cell culture and animal in vivo studies indicate the obvious effects of mechanical compression on disc cell biology. However, the effects of dynamic compression magnitude, frequency and duration on the immature nucleus pulposus (NP) from an organ-cultured disc are not well understood. OBJECTIVE: To investigate the effects of a relatively wide range of compressive magnitudes, frequencies and durations on cell apoptosis and matrix composition within the immature NP using an intelligent and mechanically active bioreactor. METHODS: Discs from the immature porcine were cultured in a mechanically active bioreactor for 7 days. The discs in various compressive magnitude groups (0.1, 0.2, 0.4, 0.8 and 1.3 MPa at a frequency of 1.0 Hz for 2 hours), frequency groups (0.1, 0.5, 1.0, 3.0 and 5.0 Hz at a magnitude of 0.4 MPa for 2 hours) and duration groups (1, 2, 4 and 8 hours at a magnitude of 0.4 MPa and frequency of 1.0 Hz) experienced dynamic compression once per day. Discs cultured without compression were used as controls. Immature NP samples were analyzed using the TUNEL assay, histological staining, glycosaminoglycan (GAG) content measurement, real-time PCR and collagen II immunohistochemical staining. RESULTS: In the 1.3 MPa, 5.0 Hz and 8 hour groups, the immature NP showed a significantly increase in apoptotic cells, a catabolic gene expression profile with down-regulated matrix molecules and up-regulated matrix degradation enzymes, and decreased GAG content and collagen II deposition. In the other compressive magnitude, frequency and duration groups, the immature NP showed a healthier status regarding NP cell apoptosis, gene expression profile and matrix production. CONCLUSION: Cell apoptosis and matrix composition within the immature NP were compressive magnitude-, frequency- and duration-dependent. The relatively high compressive magnitude or frequency and long compressive duration are not helpful for maintaining the healthy status of an immature NP.


Assuntos
Disco Intervertebral/citologia , Disco Intervertebral/fisiologia , Técnicas de Cultura de Órgãos/métodos , Animais , Apoptose , Fenômenos Biomecânicos , Reatores Biológicos , Colágeno/metabolismo , Força Compressiva , Desenho de Equipamento , Expressão Gênica , Glicosaminoglicanos/metabolismo , Disco Intervertebral/crescimento & desenvolvimento , Metaloproteinase 3 da Matriz/genética , Técnicas de Cultura de Órgãos/instrumentação , Estresse Mecânico , Sus scrofa
3.
J Orthop Res ; 35(1): 86-92, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27035885

RESUMO

Osmolarity fluctuations are inevitable within the nucleus pulposus (NP). However, the effects of osmolarity on NP cell apoptosis within the organ-cultured disc remain unclear. The objective of this study was to investigate effects of different osmolarity levels (hypo-, iso-, and hyper-) and osmolarity modes (constant and cyclic) on NP cell apoptosis in a disc perfusion culture and to study the role of the ERK1/2 pathway in this regulatory process. Porcine discs were cultured for 7 days in different osmotic medium, including constant hypo-, iso-, and hyper-osmolarity (330, 430, and 550 mOsm/L, respectively) and cyclic-osmolarity (430 mOsm/L for 8 h, followed by 550 mOsm/L for 16 h). The role of the ERK1/2 pathway was investigated by using the pharmacological inhibitor U0126. NP cell apoptosis was analyzed by TUNEL staining, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3 and protein expression of cleaved caspase-3, and cleaved PARP. Our results showed that NP cell apoptosis was increased in hypo- and hyper-osmolarity cultures compared to iso- or cyclic-osmolarity culture, whereas the level of apoptosis in the iso-osmolarity culture was lower than that in the cyclic-osmolarity culture. When the ERK1/2 pathway was inhibited in the iso- and cyclic-osmolarity cultures, the level of NP cell apoptosis was significantly increased. In conclusion, the effects of osmolarity on NP cell apoptosis depend on the osmolarity level (hypo-, iso-, or hyper-) and osmolarity mode (constant or cyclic). Futhermore, inhibition of the ERK1/2 pathway promotes NP cell apoptosis in this process. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:86-92, 2017.


Assuntos
Apoptose , Sistema de Sinalização das MAP Quinases , Núcleo Pulposo/fisiologia , Animais , Caspase 3/metabolismo , Marcação In Situ das Extremidades Cortadas , Masculino , Concentração Osmolar , Biossíntese de Proteínas , Suínos , Técnicas de Cultura de Tecidos
4.
PLoS One ; 8(12): e83951, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24391852

RESUMO

BACKGROUND: Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease. AIM: To evaluate whether IR was related to ED in young adult patients. METHODS: A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD). RESULTS: IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED. CONCLUSIONS: Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.


Assuntos
Artéria Braquial/patologia , Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Resistência à Insulina , Adulto , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Disfunção Erétil/metabolismo , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Fatores de Risco , Testosterona/metabolismo , Triglicerídeos/metabolismo
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 27(3): 185-91, 2006 Mar.
Artigo em Zh | MEDLINE | ID: mdl-16792880

RESUMO

OBJECTIVE: In mid-July 2005, five patients presented with septic shock to a hospital in Ziyang city in Sichuan, China, to identify the etiology of the unknown reason disease, an epidemiological, clinical, and laboratory study were conducted. METHODS: An enhanced surveillance program were established in Sichuan, the following activities were introduced: active case finding in Sichuan of (a) laboratory diagnosed Streptococcus suis infection and (b) clinically diagnosed probable cases with exposure history; supplemented by (c) monitoring reports on meningococcal meningitis. Streptococcus suis serotype 2 infection was confirmed by culture and biochemical reactions, followed by sequencing for specific genes for serotype and virulence factors. RESULTS: From June 10 to August 21, 2005, 68 laboratory confirmed cases of human Streptococcus suis infections were reported. All were villagers who gave a history of direct exposure to deceased or sick pigs in their backyards where slaughtering was performed. Twenty six (38%) presented with toxic shock syndrome of which 15 (58%) died. Other presentations were septicaemia or meningitis. All isolates were tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef and sly. There were 136 clinically diagnosed probable cases with similar exposure history but incomplete laboratory investigations. CONCLUSION: An outbreak of human Streptococcus suis serotype 2 infections occurred in villagers after direct exposure to deceased or sick pigs in Sichuan. Prohibition of slaughtering in backyards brought the outbreak to a halt. A virulent strain of the bacteria is speculated to be in circulation, and is responsible for the unusual presentation of toxic shock syndrome with high case fatality.


Assuntos
Surtos de Doenças , Choque Séptico/epidemiologia , Choque Séptico/microbiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/isolamento & purificação , Animais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , China/epidemiologia , Humanos , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Infecções Estreptocócicas/veterinária , Suínos , Doenças dos Suínos/microbiologia
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